Although hepatic phenylalanine hydroxylase occurs as a mixture of dimer and tetramers, it is the dimeric form that is catalytically active. Activation of phenylalanine hydroxylase by phenylalanine is accompanied by an increased interaction between the monomers. The human hydroxylase is in a highly activated state. Human phenylalanine hydroxylase has an unexpectedly high affinity for phenylalanine.